Myosin binding protein-C limits strain induced cross-bridge detachment in response to rapid stretch in cardiac and skeletal muscle

MyBP-C is a family of regulatory proteins found in muscle sarcomeres, where they regulate contraction and relaxation. Mutations in all MyBP-C paralogs cause disease in skeletal and cardiac muscles. We used a powerful "cut and paste" strategy to selectively remove MyBP-C from slow-twitch, fast-twitch, and cardiac muscle to show that each MyBP-C effects cross-bridge behavior similarly, though to varying degrees. Each MyBP-C had a notable effect on transient responses to rapid stretch, where MyBP-C was found to limit strain-induced cross-bridge detachment, especially in fast-twitch muscles. Strain-induced cross-bridge detachment is critical for rapid filling of the left ventricle in diastole and for sustained contraction in skeletal muscle. MyBP-C paralogs appear adapted to meet the mechanical demands of each muscle type.